Comfortis Chewable Tablets (140 mg)

COMFORTIS (spinosad) is available in four sizes of chewable flavoured tablets for oral administration to cats and kittens according to their weight. Each chewable flavoured tablet is formulated to provide a minimum spinosad dosage of 50 mg/kg. COMFORTIS chewable tablets (spinosad) are available in six sizes of chewable flavoured tablets for oral administration to dogs and puppies 14 weeks of age and older according to their weight. Each chewable tablet is formulated to provide a minimum spinosad dosage of 30 mg/kg. Spinosad is a member of the class of antiparasitics, spinosyns, which are novel non-antibacterial tetracyclic macrolides. Spinosad contains two major factors, spinosyn A and spinosyn D, derived from the naturally occurring bacterium, Saccharopolyspora spinosa.

Indication:

COMFORTIS kills fleas and is indicated for the prevention and treatment of flea infestations (Ctenocephalides felis) on cats and dogs for one month.

Dosage and Administration

Cats - COMFORTIS is given orally once a month, at the minimum dosage of 50 mg/kg and a maximum of 100 mg/kg.

Do not use the dosing schedule below when administering COMFORTIS to dogs, as it can result in overdosage.

Dosage Schedule - Cats:

Body Weight (kg)

Spinosad Per Tablet (mg)

Tablets Administered

0.9 to 1.8

90

One

1.9 to 2.7

140

One

2.8 to 5.4

270

One

5.5 to 10.9*

560

One

*Cats over 10.9 kg should be administered the appropriate combination of tablets.

Dogs - COMFORTIS chewable tablets are given orally once a month, at the recommended minimum dosage of 30 mg/kg to a maximum of 60 mg/kg.

Recommended Dosage Schedule - Dogs:

Body Weight (kg)

Spinosad Per Tablet (mg)

Tablets Administered

1.5 to 2.2

90

One

2.3 to 4.5

140

One

4.6 to 9.1

270

One

9.2 to 18.2

560

One

18.3 to 27.2

810

One

27.3 to 54.5*

1620

One

*Dogs over 54.5 kg should be administered the appropriate combination of tablets.

Administer COMFORTIS with food for maximum effectiveness.

COMFORTIS is a chewable tablet and is readily consumed by cats and dogs when offered by the owner just prior to feeding. Alternatively, COMFORTIS may be offered in food or administered like other tablet medications. COMFORTIS should be administered at monthly intervals.

If vomiting occurs within an hour of administration, redose with another full dose. If a dose is missed, administer COMFORTIS with food and resume a monthly dosing schedule.

Treatment with COMFORTIS may begin at any time of the year. For prevention of flea infestations COMFORTIS should be administered preferably starting one month before fleas become active and administered at regular monthly intervals through the end of flea season. For maximum efficacy, it is important to dose COMFORTIS on a consistent, monthly interval during seasonal periods of flea activity.

To minimize the likelihood of flea reinfestation, it is important to treat all animals within a household with an approved flea product.

Cautions:

Cats - Comfortis is for cats 14 weeks of age and older and a body weight of 900 g or greater (see Animal Safety).

Use with caution with concomitant extra label use of ivermectin (see Adverse Reactions).

The safe use of COMFORTIS in breeding, pregnant, lactating cats and cats less than 14 weeks of age has not been evaluated.

Dogs - Use of COMFORTIS concurrently with ivermectin at any dose other than the approved label dose for heartworm prophylaxis should be avoided. Concurrent use of COMFORTIS with high extra-label doses of ivermectin for parasitic mange or demodicosis has been associated with an increased risk of developing neurological signs typically associated with ivermectin toxicity.

Use of COMFORTIS in dogs with a history of epilepsy or seizures should be avoided. COMFORTIS should only be administered to dogs with a history of epilepsy or seizures under the supervision of a veterinarian, and where alternative therapies are not appropriate or likely to be efficacious.

COMFORTIS is for use in dogs and puppies 14 weeks of age and older (see ANIMAL SAFETY).

Use with caution in breeding females (see ANIMAL SAFETY). The safe use of COMFORTIS in breeding males has not been evaluated.

Warning

Keep out of reach of children.

Adverse Reactions

Cats - In a well-controlled US field study, which included a total of 211 cats (139 treated with COMFORTIS and 72 treated with an active topical control once a month for 3 treatments), no serious adverse reactions were attributed to the administration of COMFORTIS.

Over the 90-day study period, all observations of potential adverse reactions were recorded. Reactions that occurred at an incidence >1% within any of the 3 months of observations are presented in the following table. The most frequently reported adverse reaction in cats was vomiting.

Percentage of Cats with Adverse Reactions

Adverse Reaction

Month 1

Month 2

Month 3

COMFORTIS
(n=139)

Active Topical Control
(n=72)

COMFORTIS
(n=135)

Active Topical Control
(n=69)

COMFORTIS
(n=132)

Active Topical Control
(n=67)

Vomiting

14.4

1.4

14.8

1.4

13.6

4.5

Lethargy

3.6

0.0

0.7

0.0

1.5

1.5

Anorexia

2.2

0.0

0.7

0.0

2.3

1.5

Weight Loss

1.4

0.0

0.0

0.0

3.0

0.0

Diarrhea

1.4

1.4

0.7

2.9

2.3

1.5

Over the 3-month (3-dose) study, vomiting occurred on the day of or the day after at least one dose in 28.1% (39/139) of the cats treated with COMFORTIS and in 2.8% (2/72) of the cats treated with the active topical control. Three of 139 cats treated with COMFORTIS vomited on the day of or the day after all three doses.

Two cats that received extra label topical otic ivermectin on Day -1 of the field study developed lethargy on Day 1 after COMFORTIS administration on Day 0.

For technical assistance or to report an adverse drug experience, call 1-800-265-5475.

Dogs - In dogs, the most frequently reported adverse event is vomiting, which most commonly occurs in the first 48 hours after dosing. In the majority of cases, vomiting is transient, mild and does not require symptomatic treatment. Other adverse reactions in dogs are uncommon or rare, and include depression/lethargy, anorexia, diarrhoea, ataxia, pruritus, trembling, hypersalivation and seizures.

Following concomitant extra-label use of ivermectin with COMFORTIS, some dogs have experienced the following clinical signs: trembling/twitching, salivation/drooling, seizures, ataxia, mydriasis, blindness and disorientation. Post approval experience continues to support the safety of COMFORTIS when used concurrently with heartworm preventatives according to label directions.

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinarian.

Mode of Action:

The primary target of action of COMFORTIS in insects is an activation of nicotinic acetylcholine receptors (nAChRs). Spinosad does not interact with known insecticidal binding sites of other nicotinic or GABAergic insecticides such as neonicotinoids, fiproles, milbemycins, avermectins, and cyclodienes. Insects treated with spinosad show involuntary muscle contractions and tremors resulting from activation of motor neurons. Prolonged spinosad-induced hyperexcitation results in prostration, paralysis, and flea death. The selective toxicity of spinosad between insects and vertebrates may be conferred by the differential sensitivity of the insect versus vertebrate nAChRs.

Effectiveness

Cats - In a well-controlled laboratory study, COMFORTIS began to kill fleas 30 minutes after administration and demonstrated 85% effectiveness1 at 4 hours and 91% effectiveness by 8 hours. COMFORTIS kills fleas before they can lay eggs. In one well-controlled laboratory study using a US strain of fleas, COMFORTIS demonstrated 100% effectiveness on the first day following treatment and 77% effectiveness on Day 30; however, two cats vomited following dosing and were not re-dosed. In two well-controlled laboratory studies using European strains of fleas, COMFORTIS demonstrated 100% effectiveness on the first day of treatment and >98% and 94% effectiveness on Day 30.

If a severe environmental infestation exists, fleas may persist for a period of time after dose administration due to the emergence of adult fleas from pupae already in the environment.

In a field study conducted in households with existing flea infestations, flea count reductions of 92.6% were observed one month after the first treatment and 97.5% after three monthly treatments with COMFORTIS. Cats with pre-existing signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis, and pruritus as a direct result of eliminating the fleas.

1Calculated Using Arithmetic Means

Dogs - In a well-controlled laboratory study, COMFORTIS began to kill fleas 30 minutes after administration and demonstrated 100% effectiveness within 4 hours. COMFORTIS kills fleas before they can lay eggs which are precursors to pupae. If a severe environmental infestation exists, fleas may persist for a period of time after dose administration due to the emergence of adult fleas from pupae already in the environment. In field studies conducted in households with existing flea infestations of varying severity, flea reductions of 98.0% to 99.8% were observed over the course of 3 monthly treatments with COMFORTIS.

Dogs with signs of Flea Allergy Dermatitis (FAD), including erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus showed improvement as a direct result of eliminating fleas.

Animal Safety:

Cats - In a margin of safety study, COMFORTIS was administered orally to 14-week-old kittens at 1X, 3X, and 5X the upper half (75-100 mg/kg) of the therapeutic dose band for six monthly dosing intervals 28 days apart. Vomiting was observed across all groups, but was seen with greater frequency in cats in the treated groups; it did not increase with increasing doses. Loose stool was observed in all but the 3X treatment group. Food consumption was decreased in the 5X female cats. COMFORTIS was not associated with clinically significant changes in hematology, clinical chemistry, coagulation, or urinalysis parameters. Minor elevations were seen in ALT, AST and cholesterol values in clinical chemistry but were not associated with any clinical signs. Cats demonstrated cytoplasmic vacuolation, consistent with phospholipidosis, in the liver, lung, and adrenal gland. The long term effects of phospholipidosis are unknown. One cat in the 3X group had an enlarged thyroid/parathyroid gland found at necropsy. Higher liver weights occurred in cats in the 3X and 5X group that correlated with hepatocellular vacuolation and hypertrophy. There was no indication of any detrimental effects based on clinical chemistries and anatomical changes. The administration of COMFORTIS was not associated with any clinically significant, gross necropsy or histopathological changes.

In a well-controlled field study, COMFORTIS was administered in conjunction with other frequently used veterinary products, including tapeworm anthelmintics, antibiotics, and an approved heartworm preventative containing ivermectin. Hematology and clinical chemistry values were compared pre- and post-study and were unremarkable.

Dogs - COMFORTIS were tested in 91 different pure and mixed breeds of healthy dogs in well-controlled clinical and laboratory studies. No dogs were withdrawn from the field studies due to treatment-related adverse reactions.

In a dose tolerance safety study, COMFORTIS was administered orally to adult Beagle dogs at a dose range of 81-98.8 mg/kg once daily for 10 consecutive days (16.7 times the maximum recommended monthly dose). Vomiting was seen in 5 of 6 treated dogs during the first 6 days of treatment, usually within 2.5 hours of dosing. Treated females lost weight early in the treatment period, but their weights were similar to control dogs by the end of the 24-day study. COMFORTIS was not associated with any clinically significant changes in hematology, blood coagulation or urinalysis parameters; however, mild elevations in ALT occurred in all dogs treated with COMFORTIS. By day 24, ALT values had returned to near baseline levels. Phospholipidosis (vacuolation) of the lymphoid tissue was seen in all dogs treated with COMFORTIS, the long term effects of which are unknown.

In a margin of safety study, COMFORTIS were administered orally to 6-week-old Beagle puppies at average doses of 1.5, 4.4, and 7.4 times the maximum recommended dose at 28-day intervals over a 6-month period. Vomiting was observed across all groups, including the placebo. Increased vomiting was observed at elevated doses, usually within 1 hour following administration. Vomiting at all doses decreased over time and stabilized when puppies were 14 weeks of age. The average daily and total weight gains of treated dogs were smaller than control dogs and were dose dependent. COMFORTIS was not associated with clinically significant changes in hematology, clinical chemistry, coagulation or urinalysis parameters. Phospholipidosis (vacuolation) of the lymphoid tissue was seen in some dogs in the 4.4 X group and all dogs in the 7.4 X group. The long term effects of phospholipidosis are unknown. Treatment with COMFORTIS was not associated with any other clinically significant adverse clinical observations, gross necropsy or histopathological changes.

In a reproductive safety study, COMFORTIS was administered orally to female Beagles at 1.3 and 4.4 times the maximum recommended therapeutic dose every 28 days prior to mating, during gestation, and during a six-week lactation period. No treatment-related adverse effects were noted for conception rates in the dams, or for mortality, body temperature, necropsy or histopathology findings for the dams or puppies. One dam from each treatment group experienced early pregnancy loss and one additional high dose dam aborted late term. The treated dams experienced more vomiting, especially at one hour post-dose, than the control dams. Puppies from dams treated at 1.3 times the maximum recommended therapeutic dose had lower body weights than puppies from control dams. Although puppy mortality between treated and control dams was not different, the puppies from the treated dams experienced more lethargy, dehydration, weakness and felt cold to the touch (4.4 X group only) when compared to puppies from control dams.

A pilot study without a control group was conducted to analyze milk from three lactating dogs treated with an experimental formulation of spinosad at 1.5 times the maximum recommended dose administered at day 28 of gestation and 24 hours prior to parturition. The data demonstrated that spinosyns were excreted in the milk of these dogs. Mortality and morbidity were highest in puppies from the one dam where spinosyns in milk were highest. The spinosad milk:blood exposure ratio calculated from this study ranged from 2.2 to 3.5.

In well-controlled field studies, COMFORTIS was administered in conjunction with other frequently used veterinary products, such as vaccines, anthelmintics, antiparasitics, antibiotics, steroids, tick control products, anesthetics, NSAIDs, antihistamines, alternative/herbal remedies, shampoos, prescription diets, and most generally prescribed medications. Changes in hematology, clinical chemistry and urinalysis values were compared pre- and post-study and were unremarkable.

Storage

Store at 20-25°C. Excursions permitted between 15-30°C.

How Supplied

COMFORTIS is available in six flavoured tablet sizes: 90, 140, 270, and 560 mg for both cats and dogs; 810 and 1620 mg for dogs. Each tablet size is available in colour-coded packages of 6 tablets.

Comfortis, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.

Every effort has been made to ensure the accuracy of the Comfortis Chewable Tablets (140 mg) information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.